SYNTHETIC ALPHA,BETA-(1-]4)-GLUCAN OLIGOSACCHARIDES AS MODELS FOR HEPARAN-SULFATE

alpha,beta-(1-->4)-Glucans were devised as models for heparan sulfate with the simplifying assumptions that carboxyl-reduction and sulfation of heparan sulfate does not decrease the SMC antiproliferative activity and that N-sulfates in glucosamines can be replaced by O-sulfates. The target oligosaccharides were synthesized using maltosyl building blocks. Glycosylation of methyl 2,3,6,2',3',6'-hexa-O-benzyl-beta-maltoside (1) with hepta-O-acetyl-alpha-maltosyl bromide (2) furnished tetrasaccharide 3 which was deprotected to alpha-D-Glc-(1-->4)-beta-D-Glc-(1-->4)-alpha-D-Glc-(1-->4)-beta-D-Glc-(1-->OCH3) (5) or, alternatively, converted to the tetrasaccharide glycosyl acceptor (8) with one free hydroxyl function (4 ''''-OH). Further glycosylation with glucosyl or maltosyl bromide followed by deblocking gave the pentasaccharide [beta-D-Glc-(1-->4)-alpha-D-Glc-(1-->)](2)-beta-D-Glc-(1-->OCH3) (11) and hexasaccharide [alpha-D-Glc-(1-->4)-beta-D-Glc-(1-->4)](2)-alpha-D-Glc-(1-->4)-beta-D-Glc-(1-->OCH3) (14). The protected tetrasaccharide 3 and hexasaccharide 12 were fully characterized by H-1 and C-13 NMR spectroscopy. Assignments were possible using 1D TOCSY, T-ROESY, H-1,H-1 2D COSY supplemented by H-1-detected one-bond and multiple-bond H-1, C-13 2D COSY experiments.